a molecular dynamics (md) and quantum mechanicsmolecular mechanics (qmmm) study on ornithine cyclodeaminase (ocd) a tale of two iminiums分子动力学(md)和量子mechanicsmolecular力学(qmmm)研究鸟氨酸cyclodeaminase(ocd)两个iminiums的故事.pdfVIP

Int. J. Mol. Sci. 2012, 13, 12994-13011; doi:10.3390/ijms131012994 OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Article A Molecular Dynamics (MD) and Quantum Mechanics/Molecular Mechanics (QM/MM) Study on Ornithine Cyclodeaminase (OCD): A Tale of Two Iminiums Bogdan F. Ion, Eric A. C. Bushnell, Phil De Luna and James W. Gauld * Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada; E-Mails: ionb@uwindsor.ca (B.F.I.); bushne1@uwindsor.ca (E.A.C.B.); deluna@uwindsor.ca (P.D.L.) * Author to whom correspondence should be addressed; E-Mail: gauld@uwindsor.ca; Tel.: +1-519-253-3000; Fax: +1-519-973-7098. Received: 10 September 2012; in revised form: 27 September 2012 / Accepted: 27 September 2012 / Published: 11 October 2012 + Abstract: Ornithine cyclodeaminase (OCD) is an NAD -dependent deaminase that is found in bacterial species such as Pseudomonas putida. Importantly, it catalyzes the direct conversion of the amino acid L-ornithine to L-proline. Using molecular dynamics (MD) and a hybrid quantum mechanics/molecular mechanics (QM/MM) method in the ONIOM formalism, the catalytic mechanism of OCD has been examined. The rate limiting step is calculated to be the initial step in the overall mechanism: hydride transfer from the